Polyglutamine-binding protein 1 (PQBP1)

Polyglutamine-binding protein 1 (PQBP1) is a nuclear protein encoded by the *PQBP1* gene located on the X chromosome. It is characterized by a WW domain—mediating protein-protein interactions—and a highly degenerate, intrinsically disordered C-terminal domain. PQBP1’s primary molecular functions involve regulation of pre-mRNA splicing and gene transcription through interactions with RNA polymerase II and spliceosome components. PQBP1 also participates in the formation of RNA granules within neurons, facilitating RNA storage and regulated translation. Genetically, it is notable for its involvement in X-linked intellectual disability syndromes such as Renpenning syndrome, with pathogenic mutations typically leading to loss of function, and thus impaired neuronal RNA processing and development. PQBP1 also interacts with— and is affected by—pathogenic proteins seen in neurodegenerative diseases (such as mutant Ataxin-1, Huntingtin, and tau), further linking RNA dysregulation and protein misfolding to disease pathogenesis. Recent studies implicate PQBP1 as an adaptor protein mediating innate immune detection of retroviruses (HIV-1) and pathologic tau aggregates in microglia, where PQBP1 can act as an intracellular pathogen and damage sensor. There are currently no drugs developed to directly target PQBP1, nor does it fall into categories such as receptor, enzyme, or transporter.

Other names

Polyglutamine tract-binding protein 1NPW38JM26PQBP-1Npw3838 kDa nuclear protein containing a WW domainMRX2MRX55MRXS3MRXS8RENS1SHS